title: Enhancement of hypoxia-induced gene expression in fish liver by the aryl hydrocarbon receptor (AhR) ligand, benzo[a]pyrene (BaP).
abstract: Fish in polluted coastal habitats commonly suffer simultaneous exposure to both hypoxia and xenobiotics. Although the adaptive molecular responses to each stress have been described, little is known about the interaction between the signaling pathways mediating these responses. Previous studies in mammalian hepatoma cell lines have shown that hypoxia-inducible factor (HIF)- and/or aryl hydrocarbon receptor (AhR)-activated gene expression is suppressed following co-exposure to hypoxia and the hallmark AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, whether similar crosstalk exists in the non-tumor liver tissues of fish and whether other non-TCDD ligands also play the same inhibitory role in this crosstalk remain unknown. Here, the in vivo hepatic mRNA expression profiles of multiple hypoxia- and AhR-responsive genes (later gene expression=mRNA expression of the gene) were examined in the orange-spotted grouper (Epinephelus coioides) upon single and combined exposures to hypoxia and benzo[a]pyrene (BaP). Combined exposure enhanced hypoxia-induced gene expression but did not significantly alter BaP-induced gene expression. Protein carbonyl content was markedly elevated in fish subjected to combined exposure, indicating accumulation of reactive oxygen species (ROS). Application of diethyldithiocarbamate (DDC) to hypoxia-treated grouper liver explants similarly exaggerated hypoxia-induced gene expression as in the combined stress tissues in vivo. These observations suggest that ROS derived from the combined hypoxia and BaP stress have a role in enhancing hypoxia-induced gene expression.
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.
authors.forename: Richard Man Kit
authors.initials: RM
authors.lastname: Yu
authors.forename: Patrick Kwok Shing
authors.initials: PK
authors.lastname: Ng
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Tan
authors.forename: Daniel Ling Ho
authors.initials: DL
authors.lastname: Chu
authors.forename: Rudolf Shiu Sun
authors.initials: RS
authors.lastname: Wu
authors.forename: Richard Yuen Chong
authors.initials: RY
authors.lastname: Kong
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D008658:Inactivation, Metabolic / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009924:Organ Culture Techniques; D010473:Perciformes / Q000378:metabolism*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene; D013482:Superoxide Dismutase